Nivolumab retreatment in non-small cell lung cancer patients who responded to prior immune-checkpoint inhibitors and had ICI-free intervals (WJOG9616L)

• Published in: Clinical cancer research 2022-05, Vol.28 (15), p.3207-3213
• Main Authors: Akamatsu, Hiroaki, Teraoka, Shunsuke, Takamori, Shinkichi, Miura, Satoru, Hayashi, Hidetoshi, Hata, Akito, Toi, Yukihiro, Shiraishi, Yoshimasa, Mamesaya, Nobuaki, Sato, Yuki, Furuya, Naoki, Oyanagi, Jun, Koh, Yasuhiro, Misumi, Toshihiro, Yamamoto, Nobuyuki, Nakagawa, Kazuhiko
• Format: Article
• Language: English
• Subjects: Research Briefs: Clinical Trial Brief Reports
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-22-0602

To explore the efficacy of retreatment with immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients who responded to prior ICI and had adequate ICI-free interval. Advanced NSCLC patients who had achieved complete response (CR), partial response (PR), or stable disease for {greater than or equal to}6 months with prior ICI therapy preceding progression were prospectively enrolled. All patients should have had ICI-free interval {greater than or equal to} 60 days before registration. Patients were treated with nivolumab (240 mg/body) every 2 weeks until progression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival, and safety (Trial Identifier, UMIN000028561). Sixty-one patients were enrolled during October 2017-February 2020, with 59 analyzed for efficacy. Regarding prior ICI, 41 patients had CR or PR. Median treatment on ICI and median ICI-free intervals were 8.1 months and 9.2 months, respectively. Twenty patients experienced immune-related adverse events (irAEs) that required discontinuation of prior ICI. Nivolumab retreatment demonstrated ORR of 8.5% (95% confidence interval [CI]: 2.8-18.7%) and median PFS of 2.6 months (95% CI: 1.6-2.8 months) while five responders had 11.1 months of median PFS. In the multivariate analysis, ICI-free interval was the only predictive factor of PFS (hazard ratio: 2.02, p = 0.02), while prior efficacy or history of irAE was not. Common adverse events were skin disorders (23%), malaise (20%), and hypoalbuminemia (15%). Even in patients who initially responded to prior ICI and had ICI-free interval, once resistance occurred, retreatment with nivolumab had limited efficacy.